p70S6 Kinase

mTOR is a serine/threonine protein kinase and part of the phosphoinositide-3-kinase (PI3K) signalling pathway which plays a pivotal role in cancer. The therapeutic potential for inhibiting this pathway has driven considerable R&D efforts during the last 20 years culminating in clinical trials of many pathway inhibitors [Nature Reviews Cancer 9, 550-562 (2009) ] and the approval of Temsirolimus (CCI-779) for the treatment of advanced renal cell carcinoma [J Urol 177, 346-52 (2007)].

The enzyme, p70S6 kinase (p70S6K) is a serine-threonine kinase and is phosphorylated by mTORC1 promoting mRNA translation by the phosphorylation and activation of the S6 ribosomal protein.  p70S6K has been implicated in ovarian cancer [Oncogene 1-13 (2011)] & breast cancer [Mol Cancer Ther, 9(5) (2010)] and has been shown to be required for tumour growth and angiogenesis through HIF-1a and VEGF expression [Biochemical and Biophysical Research Communications 398, 395–399 (2010)].  Inhibitors of p70S6K have promise not only as single agents but in combination with other targeted therapeutics.
 

PI3K signals through AKT to activate mTOR leading to phosphorylation and activation of p70S6K which promotes protein translation, cell invasion and cell growth

Sentinel Oncology is seeking partners to develop first in class, selective p70S6K inhibitors.

To learn more about the programme please contact us